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G-quadruplex DNA Structures and Genome Stability

Objective

Secondary structures such as G-quadruplexes (G4s) can form within DNA or RNA. They pose a dramatic risk for genome stability, because due to their stability they can block DNA replication and this could lead to DNA breaks. In certain cancer cells mutations/deletions are observed at G4s, if a helicase that is important for G4 unwinding is mutated. Nevertheless, G4s are also discussed to be functional elements for cellular processes such as telomere protection, transcription, replication, and meiosis. The aim of this research proposal is to use various biochemical and computational tools to determine which proteins are essential for formation and regulation of G4s. Proposed experiments will gain insights into both “effects” of G4s, the risk for genome stability and its significant function for the cell. In aim 1 we will elucidate and identify novel proteins that bind, regulate, and repair G4s, especially in the absence of helicases, in vitro and in vivo. Our focus is to understand how G4s become mutated in the absence of helicases, which proteins are involved, and how genome stability is preserved. In aim 2, we will use cutting edge techniques to identify regions that form G4s in vivo. Although there is experimental proof for G4s in vivo, this is not commonly accepted, yet. We will provide solid data that will support the existence of G4s in vivo. Furthermore, we will survey genome-wide when and why G4s become a risk for genome stability. Aim 3 will focus on the in silico observation that G4 structures are connected to meiosis. In this aim we will use a combination of techniques to unravel the biological significance of G4s during meiosis in vivo.
Due to the connection of G4s and cancer the data obtained from this research proposal will not only be important to understand G4 regulation and formation, but will also provide unique knowledge on the impact of G4 structures for genome stability and thereby for human health.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2014-STG

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Host institution

UNIVERSITATSKLINIKUM BONN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 119 382,12
Address
VENUSBERG-CAMPUS 1
53127 Bonn
Germany

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Region
Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 119 382,12

Beneficiaries (3)

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